Abstract: :
Purpose: We previously reported that Tlx, an orphan nuclearreceptor, knockout(KO)mouse showed the phenotype of retinaldegeneration and impaired vasculogensis. In the present study,we investigated how and by which cell type Tlx plays roles inthe control of retinal development and vasculogensis.Methods: We first identified the cells by which Tlx is expressedthrough the use of lacZ knock–in marker and retinal specificantibodies. The process of retinal degeneration of Tlx KO mousewas analyzed by light microscopy, electron microscopy and TUNELmethod. The process of impaired vasculogenesis was also analyzedby immunohistochemistry. To examine if the retinal ischemiawas involved in the retinal degeneration, explant culture ofTlx KO retina was conducted.Results:Tlx expression was initially located in the retinalprogenitor cells and then confined to Müller glial cellsduring the postnatal stage. Tlx was also expressed transientlyby retinal astrocytes migrating over the inner surface of retina.The lack of Tlx led to the defect in the regulation of cellnumbers at each nuclear layer and hypoplasia of Müllercells. The delayed migration and impaired network formationof astrocyte over the retina was observed in Tlx KO retina,which preceded the lack of vasculogenesis.Conclusions: Tlx appears to regulate the proper numbers of distinctneuronal subtypes at each nuclear layer and is required forthe development of Müller cells and astrocytes. The regulationof the retina–intrinsic and –extrinsic developmentalprograms by Tlx is critical for the proper retinal organization.